Download 3. pharmapeutical form - Veterinary Medicines Directorate

Revised: May 2016
AN: 00762/2015
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE VETERINARY MEDICINAL PRODUCT
DORAFLOX 100 mg/ml solution for injection for cattle and pigs
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains:
Active substance
Enrofloxacin
100 mg
Excipients
Benzyl alcohol
Disodium edetate
7.8 mg
10 mg
For the full list of excipients, see section 6.1.
3. PHARMAPEUTICAL FORM
Solution for injection.
Clear slightly yellowish solution.
4. CLINICAL PARTICULARS
4.1 Target species
Cattle and pigs.
4.2 Indications for use, specifying the target species
Cattle
Treatment of infections of the respiratory tract caused by enrofloxacin susceptible
strains of Pasteurella multocida, Mannheimia haemolytica and Mycoplasma spp.
Treatment of acute severe mastitis caused by enrofloxacin susceptible strains of
Escherichia coli.
Treatment of infections of the alimentary tract caused by enrofloxacin susceptible
strains of Escherichia coli.
Treatment of septicaemia caused by enrofloxacin susceptible strains of
Escherichia coli.
Treatment of acute mycoplasma-associated arthritis due to enrofloxacin
susceptible strains of Mycoplasma bovis in cattle less than 2 years old.
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Pigs
Treatment of infections of the respiratory tract caused by enrofloxacin susceptible
strains of Pasteurella multocida, Mycoplasma spp. and Actinobacillus
pleuropneumoniae.
Treatment of infections of the urinary tract caused by enrofloxacin susceptible
strains of Escherichia coli.
Treatment of post-partum dysgalactiae syndrome, PDS (MMA syndrome) caused
by enrofloxacin susceptible strains of Escherichia coli and Klebsiella spp.
Treatment of infections of the alimentary tract caused by enrofloxacin susceptible
strains of Escherichia coli.
Treatment of septicaemia caused by enrofloxacin susceptible strains of
Escherichia coli.
4.3 Contra-indications
Do not use in growing horses because of possible deleterious damage on articular
cartilage.
Do not use for prophylaxis.
Do not use when resistance / cross resistance to (Fluoro)quinolones is known to
occur.
Refer to section 4.5. Do not use in the case of known hypersensitivity to
fluoroquinolones or to any of the excipients.
4.4 Special warnings for each target species
None known.
4.5 Special precautions for use
Special precautions for use in animals
Degenerative changes of articular cartilage were observed in calves treated orally
with 30 mg enrofloxacin/kg bw during 14 days.
Do not exceed the recommended dose.
Repeat injections should be administered at different sites.
Enrofloxacin should be used with caution in epileptic animals or animals affected
by renal dysfunction.
Official and local antimicrobial policies should be taken into account when the
product is used.
Fluoroquinolones should be reserved for the treatment of clinical conditions which
have responded poorly, or are expected to respond poorly, to other classes of
antimicrobials.
Whenever possible, fluoroquinolones should only be used based on susceptibility
testing.
Use of the product deviating from the instructions given in the SPC may increase
the prevalence of bacteria resistant to the fluoroquinolones and may decrease the
effectiveness of treatment with other quinolones due to the potential for cross
resistance.
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The use of enrofloxacin in growing lambs at the recommended dose for 15 days
caused histological changes in the articular cartilage, not associated with clinical
signs.
Special precautions to be taken by the person administering the veterinary
medicinal product to animals
The product is an alkaline solution. Wash any splashes from skin or eyes
immediately with water.
Do not eat, drink or smoke whilst using the product.
Care should be taken to avoid accidental self-injection. If accidental self-injection
occurs seek medical advice immediately.
Direct contact with the skin should be avoided because of sensitisation, contact
dermatitis and possible hypersensitivity reactions. Wear gloves.
Other precautions
None known
4.6 Adverse reactions (frequency and seriousness)
Local tissue reactions may occasionally occur at the injection site. Normal sterile
precautions should be taken.
In cattle, gastrointestinal disturbances may occasionally occur.
4.7 Use during pregnancy, lactation or lay
There is no restriction on the use of this product during pregnancy and lactation.
4.8 Interaction with other medicinal products and other forms of interaction
Antagonistic effects due to concurrent administration of macrolides, and
tetracyclines may occur Enrofloxacin may interfere with the metabolism of
theophylline, decreasing theophylline clearance resulting in increased plasma
levels of theophylline.
4.9 Amounts to be administered and administration route
Intravenous, subcutaneous or intramuscular use.
Repeated injections should be made at different injection sites.
To ensure correct dosage, body weight should be determined as accurately as
possible to avoid underdosing.
Cattle:
5 mg of enrofloxacin/kg bw, corresponding to 1 ml/20 kg bw, once daily for 3-5
days.
Acute mycoplasma-associated arthritis due to enrofloxacin susceptible strains of
Mycoplasma bovis in cattle less than 2 years old: 5 mg of enrofloxacin/kg bw,
corresponding to 1 ml/20 kg bw, once daily for 5 days. The product can be
administered by slow intravenous or subcutaneous administration.
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Acute mastitis caused by Escherichia coli: 5 mg enrofloxacin/kg bw, corresponding
to 1 ml/20 kg bw, by slow intravenous injection once daily for two consecutive
days.
The second dose may be administered by the subcutaneous route. In this case,
the withdrawal period following subcutaneous injection applies.
Not more than 10 ml should be administered at any one subcutaneous injection
site.
Pigs:
2.5 mg of enrofloxacin/kg bw, corresponding to 0.5 ml/20 kg bw, once daily by
intramuscular injection for 3 days.
Alimentary tract infection or septicaemia caused by Escherichia coli: 5 mg of
enrofloxacin/kg bw, corresponding to 1 ml/20 kg bw, once daily by intramuscular
injection for 3 days.
In pigs, the injection should be made in the neck at the ear base.
Not more than 3 ml should be administered at one intramuscular injection site.
The stopper should not be punctured more than 20 times.
4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary
Do not exceed the recommended dose.
In accidental overdose (lethargy, anorexia) there is no antidote and treatment
should be symptomatic.
No signs of over dosage were observed in pigs following administration of the
product at five times the recommended therapeutic dose.
4.11 Withdrawal periods
Cattle:
Following intravenous injection:
Meat and offal: 5 days
Milk:
3 days
Following subcutaneous injection:
Meat and offal: 12 days
Milk:
4 days
Pigs:
Meat and offal:
13 days
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5. PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group: antibacterials for systemic use, fluoroquinolones
ATCvet-code: QJ01MA90
5.1 Pharmacodynamic properties
Mode of action
Two enzymes essential in DNA replication and transcription, DNA gyrase and
topoisomerase IV, have been identified as the molecular targets of
fluoroquinolones. Target inhibition is caused by non-covalent binding of
fluoroquinolone molecules to these enzymes. Replication forks and translational
complexes cannot proceed beyond such enzyme-DNA-fluoroquinolone
complexes, and inhibition of DNA and mRNA synthesis triggers events resulting in
a rapid, drug concentration-dependent killing of pathogenic bacteria. The mode of
action of enrofloxacin is bactericidal and bactericidal activity is concentration
dependent.
Antibacterial spectrum
Enrofloxacin is active against many Gram-negative bacteria such as Escherichia
coli, Klebsiella spp., Actinobacillus pleuropneumoniae, Mannheimia haemolytica,
Pasteurella spp. (e.g. Pasteurella multocida), against Gram-positive bacteria such
as Staphylococcus spp. (e.g. Staphylococcus aureus) and against Mycoplasma
spp. at the recommended therapeutic doses.
Types and mechanisms of resistance
Resistance to fluoroquinolones has been reported to arise from five sources, (i)
point mutations in the genes encoding for DNA gyrase and/or topoisomerase IV
leading to alterations of the respective enzyme, (ii) alterations of drug permeability
in Gram-negative bacteria, (iii) efflux mechanisms, (iv) plasmid mediated
resistance and (v) gyrase protecting proteins. All mechanisms lead to a reduced
susceptibility of the bacteria to fluoroquinolones. Cross-resistance within the
fluoroquinolone class of antimicrobials is common.
5.2 Pharmacokinetic properties
Enrofloxacin possesses a high distribution volume. Tissue levels 2-3 higher than
that found in the serum, have been demonstrated in laboratory animals and target
species. Organs in which high levels can be expected are the lungs, liver, kidney,
skin, bone and lymphatic system. Enrofloxacin also distributes into the
cerebrospinal fluid, the aqueous humour and the foetus in pregnant animals.
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6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Benzyl alcohol
Disodium edetate
Potassium hydroxide (for pH adjustment)
Glacial acetic acid
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this veterinary medicinal product must not
be mixed with other veterinary medicinal products.
6.3 Shelf-life
Shelf life of the veterinary medicinal product as packaged for sale: 2 years.
Shelf life after first opening of the immediate packaging: 28 days.
6.4. Special precautions for storage
Protect from light.
Do not freeze.
6.5 Nature and composition of immediate packaging
Type II Amber glass vials of 250 ml closed with bromobutyl rubber stoppers and
aluminium seals
One vial of 250 ml is available in a cardboard box.
Type II Amber glass vials of 100 ml closed with bromobutyl rubber stoppers and
aluminium seals
One vial of 100 ml is available in a cardboard box.
Not all pack sizes may be marketed.
6.6 Special precautions for the disposal of unused veterinary medicinal
products or waste materials
Any unused veterinary medicinal product or waste materials derived from such
veterinary medicinal product should be disposed of in accordance with local
requirements.
7. MARKETING AUTHORISATION HOLDER
Dorpharma Research B.V.
Zalmweg 24
4941 VX Raamsdonksveer
The Netherlands.
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8. MARKETING AUTHORISATION NUMBER
Vm 28365/4009
9. DATE OF FIRST AUTHORISATION
27 June 2011
10. DATE OF REVISION OF THE TEXT
May 2016
05 May 2016
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